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1.
Int J Urol ; 20(5): 522-9, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23050675

RESUMEN

OBJECTIVES: Myostatin, a member of the transforming growth factor-ß superfamily, is a negative regulator of myogenesis in skeletal muscle. We examined the effect of myostatin and myostatin inhibition by an antagonistic agent, follistatin, on growth of human urethral rhabdosphincter satellite cells (muscle stem cells) to develop a new strategy for treatment of stress urinary incontinence. METHODS: Rhabdosphincter satellite cells were cultured and selected by magnetic affinity cell sorting using an anti-neural cell adhesion molecule antibody. The cells were transfected with simian virus-40 antigen to extend their lifespan. A cell proliferation assay, a cell cycle analysis and an investigation of signal transduction were carried out. The autocrine action of endogenous myostatin by western blotting, real-time reverse transcription polymerase chain reaction and immunoneutralization using an anti-myostatin antibody was also evaluated. RESULTS: Selectively cultured cells expressed markers of striated muscles and successfully differentiated into myotubes. Myostatin inhibited proliferation of these cells through Smad2 phosphorylation and cell cycle arrest. Inhibitory effects of myostatin were reversed by addition of follistatin. However, rhabdosphincter satellite cells did not appear to use autocrine secretion of myostatin to regulate their proliferation. CONCLUSIONS: Inhibition of myostatin function might be a useful pathway in the development of novel strategies for stimulating rhabdosphincter cells regeneration to treat stress urinary incontinence.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Miostatina/farmacología , Uretra/efectos de los fármacos , Incontinencia Urinaria de Esfuerzo/tratamiento farmacológico , Comunicación Autocrina , Puntos de Control del Ciclo Celular/efectos de los fármacos , Células Cultivadas , Evaluación Preclínica de Medicamentos , Humanos , Miostatina/uso terapéutico , Transducción de Señal/efectos de los fármacos
2.
Gan To Kagaku Ryoho ; 38(10): 1627-32, 2011 Oct.
Artículo en Japonés | MEDLINE | ID: mdl-21996957

RESUMEN

We investigated the effectiveness of prophylactic FOLFOX after curative resection of synchronous metastases in patients with colorectal cancer (CRC). Clinicopathological information including postoperative chemotherapy, such as a therapeutic regimen, relapse-free survival (RFS), site of recurrence, etc., was retrospectively analyzed in 116 CRC patients with synchronous distant metastases, and 63 patients with metachronous metastases who had received surgery in our hospital between 2000 and 2009. Fifty-three patients (84%) out of 63 without adjuvant chemotherapy, and 38 (83%) out of 46 patients that received oral or intravenous 5-fluorouracil (5-FU) (alone or with leucovorin (LV)or isovorin) developed recurrent tumor(s) afterwards. The median RFSs were 119 and 281 days, respectively. By contrast, a single patient among 6 who underwent FOLFOX (up to 12 therapeutic courses) showed recurrence 476 days after surgery. The RFS of the FOLFOX was significantly higher than that of the 5-FU (+LV) or surgery alone (p=0. 03, p=0. 007, respectively). In conclusion, the FOLFOX regimen is more beneficial for CRC patients with synchronous metastasis as adjuvant chemotherapy than 5-FU (+LV) or other followup strategies.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Femenino , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/tratamiento farmacológico , Compuestos Organoplatinos/uso terapéutico , Recurrencia , Estudios Retrospectivos
3.
Oncology ; 80(1-2): 84-91, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21677451

RESUMEN

OBJECTIVES: The prophylactic effect of FOLFOX regimen, a standard regimen for unresectable colorectal cancer (CRC), was investigated in the adjuvant setting of CRC cases with distant metastases. METHODS: The study population included 116 CRC patients with synchronous metastases and 91 patients with metachronous metastases who had undergone curative operation in our hospital between 2000 and 2009. Clinicopathological parameters of CRC, postoperative chemotherapeutic regimen, recurrence rate, and relapse-free survival (RFS) were analyzed retrospectively. RESULTS: After resection of CRC and synchronous metastases, 53 (84%) out of 63 patients without chemotherapy, and 38 (83%) out of 46 that received 5-fluorouracil (5-FU) alone or with leucovorin (LV) developed recurrent tumors. By contrast, only 1 (17%) among 6 patients who underwent FOLFOX treatment showed recurrence. The FOLFOX group exhibited significantly improved RFS as compared to the 5-FU (+ LV) or surgery-alone group (p = 0.03, p = 0.007, respectively). On the other hand, in patients with metachronous metastases, tumor-relapse rate and RFS were not significantly influenced by post-metastasectomy therapies. CONCLUSIONS: In this retrospective analysis, the adjuvant administration of FOLFOX appeared to reduce the risk of relapse in a small group of CRC patients with synchronous metastases. Prospective randomized trials will be required to confirm the benefits of this management strategy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Recurrencia Local de Neoplasia , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante , Neoplasias Colorrectales/cirugía , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Estimación de Kaplan-Meier , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Modelos Logísticos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Estudios Retrospectivos , Tasa de Supervivencia
4.
J Nat Med ; 65(1): 103-10, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20890669

RESUMEN

Genus Lophophora (Cactaceae) has two species: Lophophora williamsii Coulter, which is called peyote, and L. diffusa Bravo. Although it was reported that L. williamsii contained mescaline and L. diffusa did not, we found L. williamsii specimens that did not contain mescaline. This finding indicated that the two species could not be differentiated in terms of mescaline content. Moreover, the relationship between mescaline content and morphology of the two species is also unknown. In this study, we attempted to clarify the difference in morphology, mescaline content, and DNA alignment of the chloroplast trnL/trnF region between L. williamsii and L. diffusa. As a result, L. williamsii specimens were classified into two groups. Group 1 had small protuberances on the epidermis, contained mescaline, and the analyzed region on the trnL/trnF sequence was 881 base pairs (bp) long in all except one (877 bp). Group 2 had large protuberances on the epidermis, did not contain mescaline, and the analyzed region was 893 bp long. On the other hand, L. diffusa had medium-sized protuberances on the epidermis, did not contain mescaline, and the analyzed region was 903 bp long. Also investigated was the potential application of the PCR-restriction fragment length polymorphism (RFLP) method as a means of identification based on the trnL/trnF sequence. By applying the PCR-RFLP method, the two species could be distinguished and L. williamsii specimens could be differentiated into group 1 and group 2.


Asunto(s)
Cactaceae/química , Cactaceae/genética , Mescalina/química , Cactaceae/ultraestructura , Microscopía Electrónica de Rastreo , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción
5.
J AOAC Int ; 94(6): 1770-7, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22320083

RESUMEN

An analog of aildenafil, which is a potent and highly selective inhibitor of phosphodiesterase 5, was found in a dietary supplement marketed for enhancement of sexual function. The compound was isolated by silica gel column chromatography, and its structure was identified by means of 13C-NMR spectrometry, 1H-NMR spectrometry, high-resolution MS, and X-ray structure determination. The compound was identified to be sulfoaildenafil (other names: thioaildenafil, dimethyl sildenafil thione, and thiomethisosildenafil). Sulfoaildenafil is very similar to the compound thiohomosildenafil. As it is difficult to distinguish between them by LC-photodiode array detector analysis, ultra-performance LC (UPLC)/MS, ion trap LC/MS/MS (LC/IT-MS/MS), and GC/MS were performed. The mass spectra of thiohomosildenafil by UPLC/MS and LC/IT-MS/MS showed mass fragments of m/z 58, 72, and 355, and the mass spectrum by GC/MS showed mass fragments of m/z 56, 72, and 420. Some of these fragments had low intensities, but they were useful for distinguishing between the two compounds. The relationship between aildenafil (other names: dimethylsildenafil and methisosildenafil) and homosildenafil is similar to that between sulfoaildenafil and thiohomosildenafil. Therefore, these compounds were also examined.


Asunto(s)
Suplementos Dietéticos/análisis , Piperazinas/análisis , Sulfonas/análisis , Cromatografía Liquida/métodos , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Espectroscopía de Resonancia Magnética/métodos , Estructura Molecular , Inhibidores de Fosfodiesterasa 5/análisis , Espectrometría de Masas en Tándem/métodos
6.
Anticancer Res ; 24(6): 3757-62, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15736408

RESUMEN

OBJECTIVE: Clinical studies imply that (-)-epigallocatechin-3-gallate (EGCG), a main ingredient of green tea catechins, has a chemopreventive action against cancers and suppresses the proliferation of cancer cells. However, there is no report about its chemopreventive effect for renal cancer. We previously determined that renal carcinogens suppressed the gap junction intercellular communication (GJIC) of renal epithelial cells. In this study, we investigated the effect of EGCG on the GJIC of renal epithelial cells treated with a renal carcinogen. MATERIALS AND METHODS: Mardin-Darby canine kidney (MDCK) cells were used to determine the protective effects of EGCG on dimethylnitrosamine-induced alteration of GJIC and connexin 43 (Cx 43). The maximum concentration of EGCG was determined by the lactate dehydrogenase assay method. The scrape-loading dye transfer method was used to assess the expression and cellular localization of Cx 43. The phosphorylation status of Cx 43 was determined by Western blot analysis. RESULTS: The optimal noncytotoxic concentration of EGCG was determined to be 10 microg/ml. The levels of GJIC and Cx 43 expression were markedly decreased in MDCK cells exposed to dimethylnitrosamine. A 12-h pretreatment with EGCG greatly ameliorated the GJIC-inhibitory effects of dimethylnitrosamine. CONCLUSION: These results suggest that the preservation of GJIC may indicate the chemopreventive effect of green tea on renal epithelial cells treated with a renal carcinogen in vitro.


Asunto(s)
Anticarcinógenos/farmacología , Catequina/análogos & derivados , Catequina/farmacología , Comunicación Celular/efectos de los fármacos , Uniones Comunicantes/efectos de los fármacos , Neoplasias Renales/prevención & control , Riñón/efectos de los fármacos , Té/química , Animales , Western Blotting , Carcinógenos , Transformación Celular Neoplásica/efectos de los fármacos , Conexina 43/biosíntesis , Dimetilnitrosamina , Perros , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Técnica del Anticuerpo Fluorescente , Riñón/citología , Riñón/metabolismo , Neoplasias Renales/inducido químicamente , Neoplasias Renales/patología
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